A Phase 2 interventional study of Liothyronine and Levothyroxine in Thyroid Diseases, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2015-02-23.
Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Phase 2 and Interventional
This study will examine how two thyroid preparations-levothyroxine (T4) and liothyronine (T3)-affect fat and cholesterol metabolism, blood sugar regulation, and thyrotropin secretion in patients who have had their thyroid gland removed. Results of the study may help in the development of better therapies to optimize blood sugar and cholesterol levels in some patients.
Patients 18 years of age or older who have had most or all of their thyroid gland removed and are taking long-term thyroid hormone medication may be eligible for this study after screening.
Thyroid hormone action plays an important role in the regulation of many physiologic processes, among them glucose and lipid metabolism. Interestingly, the clinical presentation of thyroid dysfunction is extremely variable, with relatively poor correlation between circulating hormone levels and clinical features. This finding suggests that the local, intracellular concentration of the active hormone liothyronine (T3), regulated by peripheral conversion of the pro-hormone levothyroxine (T4), is an important determinant in the maintenance of the thyroidal homeostasis.
The aim of the present study is the evaluation of the role of peripheral thyroid hormone conversion in the regulation of glucose and lipid metabolism by assessing the differential response to T4 or T3 treatment in subjects devoid of endogenous thyroid hormone production. T3 administration bypasses peripheral metabolism and therefore will allow us to assess the role of the peripheral thyroid hormone conversion in the regulation of the hormone action at the end-organ level.
Fifty hypothyroid subjects will be initially randomized to either of the thyroid hormone replacements liothyronine (T3) or levothyroxine (T4) treatment period (one arm cross-over design, with treatment sequence randomized), aimed to maintain serum TSH levels greater than or equal to 0.5 less than or equal to 1.5 mU/L, indicating full replacement. After a 30-day period of steady-state replacement the study subjects will be admitted to the Clinical Center and, after a three-day period of stabilization and an overnight fast, will undergo the following tests: escalating dose TRH stimulation test, indirect calorimetry, graded exercise tolerance test, DEXA scan, and echocardiogram.
Patients will also undergo skeletal muscle biopsy and subcutaneous adipose tissue biopsy and microdialysis, as well as a two-step euglycemic hyperinsulinemic clamp with measurement of splanchnic gluconeogenesis. Fasting venous blood samples will be collected for the determination of the parameters of lipid, glucose and energy metabolism.
After discharge, the patients will switch to the other form of thyroid hormone replacement therapy (second period) . The therapy will be adjusted in order to achieve the same therapeutic goal for TSH concentrations (greater than or equal to 0.5 less than or equal to 1.5 mU/L), analogous to that achieved during the first phase of the study (TSH less than or equal to 0.5 mU/L difference between T3 and T4 phases). After reaching a 30-day period of steady-state replacement, study subjects will be re-admitted to the Clinical Center and the previously described evaluation procedures will be repeated.
967 studies on the registry are indexed under Thyroid Diseases; 197 are open to participants now.
This study's enrollment of 18 is below the median of 60 across 544 interventional studies indexed under Thyroid Diseases.
Browse Thyroid Diseases studies →National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the lead sponsor of 529 studies on the registry; 54 are open to participants now.
Of its 79 completed or terminated interventional studies of FDA-regulated products, 50 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Age greater than or equal to 18 years, male or female.
History of total or near total thyroidectomy or hypothyroidism on replacement therapy.
For non-thyroidectomized patients, at least three-year history of replacement therapy (at least 1.2 mcg/Kg LT4/body weight), and less than 5% uptake at 24H on (123)I thyroid scan while on replacement therapy.
Written informed consent.
EXCLUSION CRITERIA:
BMI less than or equal to 20 or greater than or equal to 30 kg/m(2).
Metastatic thyroid cancer or history of thyroid cancer with high risk of recurrence requiring suppressive thyroid hormone therapy (Singer 1996).
Significant thyroid residual greater than 1 mL as measured by ultrasound (limited to thyroidectomized patients) or greater than 5 percent uptake at 24H on (123)I thyroid scan while on replacement therapy (limited to hypothyroid patients not undergone total thyroidectomy).
History or symptoms compatible with cardiovascular disease, including paroxysmal supraventricular tachycardia, atrial fibrillation, syncopal episodes or use of prescription medications for heart conditions, including antihypertensives.
Allergy to lidocaine, isoproterenol, TRH, levothyroxine, liothyronine, Tylenol #3, oxycodone, nitroglycerin.
Pregnancy or unwillingness to use non-hormonal contraception during the study.
Breastfeeding
Use of hormonal contraceptives or estrogen replacement therapy.
Use of tobacco (smoking, chewing) for the two weeks preceding the hospital admissions (metabolic testing)
Diabetes mellitus, either type I or II.
Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL), hypertriglyceridemia (plasma levels greater than or equal to 220 mg/dL) and/or use of antilipemic therapy.
Liver disease or ALT serum level greater than two fold the upper laboratory reference limit.
Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min.
Use of medications/supplements/alternative therapies known to alter thyroid function.
Current history or symptoms compatible with psychosis including major depression (including history of hospitalization for depression, history of attempted suicide, history of suicidal ideation).
Use of antipsychotic medications
History of drug or alcohol abuse within the last 5 years; current use of drugs or alcohol (CAGE greater than 3).
Keloid formation (relative to skeletal muscle and subcutaneous adipose tissue biopsies).
Current or previous clinically significant (requiring medical/surgical intervention) extrathyroidal manifestations of autoimmune thyroid disease (dermopathy, ophthalmopathy, arthropathy).
Hypothyroid patients treatment with Levothyroxine and Liothyronine in 2 crossover, randomized phases
Drug: Liothyronine and Levothyroxine
Hypothyroid patients are treated with Liothyronine and Levothyroxine in 2 crossover, randomized phases
Also known as: T3 and T4
Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase
Time frame: One month of therapy
Total Cholesterol at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Total Cholesterol at Liothyronine Treatment Phase
Time frame: One month of therapy.
Triglycerides at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Triglycerides at Liothyronine Treatment Phase
Time frame: One month of therapy.
Resting Energy Expenditure at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Resting Energy Expenditure at Liothyronine Treatment Phase
Time frame: One month of therapy.
Left Ventricle Mass Index at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Left Ventricle Mass Index at Liothyronine Treatment Phase
Time frame: One month of therapy.
Apolipoprotein A-I at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Apolipoprotein A-I at Liothyronine Treatment Phase
Time frame: One month of therapy.
Apolipoprotein B at Levothyroxine Treatment Phase
Time frame: One month of therapy.
Apolipoprotein B at Liothyronine Treatment Phase
Time frame: One month of therapy.
Participants recruited from NIH Clinical Center, Bethesda, Maryland, USA between June 2005 and November 2007.
| Milestone | Liothyronine First, Then Levothyroxine | Levothyroxine First, Then Liothyronine |
|---|---|---|
| Started | 7 | 7 |
| Completed | 7 | 7 |
| Not completed | 0 | 0 |
| Milestone | Liothyronine First, Then Levothyroxine | Levothyroxine First, Then Liothyronine |
|---|---|---|
| Started | 7 | 7 |
| Completed | 7 | 7 |
| Not completed | 0 | 0 |
| Milestone | Liothyronine First, Then Levothyroxine | Levothyroxine First, Then Liothyronine |
|---|---|---|
| Started | 7 | 7 |
| Completed | 7 | 7 |
| Not completed | 0 | 0 |
| mg/kg/min | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase | 7.26 ± 2.7 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Total Cholesterol at Levothyroxine Treatment Phase | 196 ± 26 |
| mg/kg/min | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase | 7.37 ± 4.4 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Total Cholesterol at Liothyronine Treatment Phase | 174 ± 28 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Triglycerides at Levothyroxine Treatment Phase | 152 ± 31 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Triglycerides at Liothyronine Treatment Phase | 144 ± 16 |
| kcal/24 hour | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Resting Energy Expenditure at Levothyroxine Treatment Phase | 1201 ± 282 |
| kcal/24 hour | Liothyronine/Levothyroxine Therapy Intervention ArmArm |
|---|---|
| Resting Energy Expenditure at Liothyronine Treatment Phase | 1177 ± 323 |
| g/m^2 | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Left Ventricle Mass Index at Levothyroxine Treatment Phase | 71 ± 16 |
| g/m^2 | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Left Ventricle Mass Index at Liothyronine Treatment Phase | 71 ± 19 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Apolipoprotein A-I at Levothyroxine Treatment Phase | 152 ± 31 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Apolipoprotein A-I at Liothyronine Treatment Phase | 144 ± 16 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Apolipoprotein B at Levothyroxine Treatment Phase | 87 ± 19 |
| mg/dl | Liothyronine/Levothyroxine Therapy Intervention Arm |
|---|---|
| Apolipoprotein B at Liothyronine Treatment Phase | 72 ± 15 |
Collected over 6 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Levothyroxine Period | — | 0/14 (0%) | 1/14 (7.1%) |
| Liothyronine Period | — | 0/14 (0%) | 0/14 (0%) |
| Event | Levothyroxine Period | Liothyronine Period |
|---|---|---|
| General disordersGeneral disorders | 0/14 | 0/14 |
| Event | Levothyroxine Period | Liothyronine Period |
|---|---|---|
| generalized anxiety disorderPsychiatric disorders | 1/14 | 0/14 |
Subjects who completed the study
| Age, Continuous(years) | Entire Study Population |
|---|---|
| Mean | 49.3 ± 8.0 |
| Sex: Female, Male(Participants) | Entire Study Population |
|---|---|
| Female | 13 |
| Male | 1 |
| Region of Enrollment(participants) | Entire Study Population |
|---|---|
| United States | 14 |
| Duration of hypothyroidism(years) | Entire Study Population |
|---|---|
| Mean | 8.6 ± 13.1 |
| Thyroid stimulating hormone (TSH)(mU/liter) | Entire Study Population |
|---|---|
| Mean | 1.1 ± 1.4 |
| Triiodothyronine (T3)(ng/dl) | Entire Study Population |
|---|---|
| Mean | 99.0 ± 24.2 |
| Free thyroxine (T4)(ng/dl) | Entire Study Population |
|---|---|
| Mean | 1.76 ± 0.46 |
This study is completed, as verified in Feb 2015. You cannot join it, but the record below documents what was studied.
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)